During high neuronal activity, the intra- and extracellular ion concentrations change. These changes affect the osmotic pressure gradients across the membranes of both neurons and astrocytes, leading to water movement and cellular swelling. We asked: Can swelling generate a hydrostatic pressure gradient of sufficient magnitude to drive non-negligible fluid flow within astrocytes or the extracellular space [1]? As it is currently infeasible to measure such intracellular pressure gradients in vivo, computational modeling emerges as a viable alternative to study the interplay between osmotic and hydrostatic forces at the microscale.  

In this study, we present a computational model of ionic electrodiffusion, hydrostatic pressures, and transmembrane- and intracompartmental fluid flow in a homogenized astrocytic syncytium surrounded by extracellular space. The model builds on previous models of ionic electrodiffusion [2,3], and potassium buffering [4]. Our findings show that increases in extracellular potassium concentrations in response to neuronal activity induce swelling and hydrostatic pressure gradients within the intra- and extracellular spaces. The fluid flow induced by these hydrostatic pressure gradients alone did not have a significant effect on the transport of potassium within any of the compartments. However, when also accounting for fluid flow induced by osmotic gradients within the astrocytic syncytium, convection played a considerable role in potassium clearance. These findings point at a mechanistic understanding of how astrocytic permeability may impact fluid flow in the brain.

[1] Halnes, G., Pettersen, K. H., Øyehaug, L., Rognes, M. E. & Einevoll, G. T. Astrocytic ion dynamics: Implications for potassium buffering and liquid flow. In Computational Glioscience, 363–391 (Springer, 2019).

[2] Mori, Y. A multidomain model for ionic electrodiffusion and osmosis with an application to cortical spreading depression. Phys. D: Nonlinear Phenom. 308, 94–108 (2015).

[3]  Zhu, Y., Xu, S., Eisenberg, R. S. & Huang, H. Optic nerve microcirculation: Fluid flow and electrodiffusion. Phys. Fluids 33, 041906 (2021).

[4] Halnes, G., Østby, I., Pettersen, K. H., Omholt, S. W. & Einevoll, G. T. Electrodiffusive model for astrocytic and neuronal ion concentration dynamics. PLoS computational biology 9, e1003386 (2013).